The lactating human mammary gland and the pancreas both produce bile salt-stimulated lipase (BSSL), a lipolytic enzyme acting on a wide range of substrates, including triglyceride, cholesterol esters, and fat-soluble vitamins esters. Breast milk BSSL has a particularly important role in the digestion of milk fat by newborn infants. We report the generation of transgenic mice that harbored a human BSSL gene controlled by a mammary gland-specific promoter. BSSL levels in transgenic mouse milk were raised to 376.8 μg/ml, corresponding to an activity of 9.15 U/ml. Premature wild-type neonates nursed by transgenic dams exhibited significantly higher survival rate than did the control neonates nursed by wild dams (95 vs. 83.3 % and, P < 0.05). They also showed 43.8 % greater body weight gain and 33.3 % lesser fecal crude fat levels than did the controls. This study provides significant evidence that increased levels of BSSL in milk may reduce mortality and improve the growth and fat absorption in premature mice during neonatal development.